Bilateral intrahippocampal aggregated beta-amyloid injection alters alternating lever cyclic-ratio schedule behavior in the rat

Aggregated β-amyloid (Aβ) in the brain is a hallmark feature of Alzheimefs disease (AD). In the current study, 12 male Sprague-Dawley rats were trained to respond under an alternating lever cyclic-ratio schedule (ALCRS) in two-lever operant chambers. The ALCRS was comprised of an ascending followed by a descending sequence of the ratio values 2, 6, 12, 20, 30, 42 and 56, and each ratio component was completed at the alternate lever. Following behavioral training, 6 rats were randomly selected as experimental subjects and 6 as control subjects. Experimental subjects received bilateral injections of 5.0 μl aggregated Aβ1-42 into the CA3 area of the hippocampus, control subjects were injected with 5.0 μl of sterile water. Aβ effects on lever switching errors, incorrect lever perseverations, and ability to track the schedule were measured for 90 days post injection. Aggregated Aβ1-42 had little effect on lever switching errors but increased lever perseveration errors, it also affected ability to track the changing parameters of the schedule. 90 days post injection subjects were sacrificed and the microglial and astrocytic response was assessed, microglia appeared to phagocytize the Aβ and astrocytes formed a barrier around the Aβ-containing microglia.